Elucidating the role of prolactin receptor during β cell adaptation to metabolic stressors
| dc.contributor.advisor | Huang, Carol | |
| dc.contributor.author | Lee, Daniel | |
| dc.contributor.committeemember | Hemberger, Myriam | |
| dc.contributor.committeemember | Shemanko, Carrie | |
| dc.date | 2024-05 | |
| dc.date.accessioned | 2024-05-07T14:42:53Z | |
| dc.date.available | 2024-05-07T14:42:53Z | |
| dc.date.issued | 2024-05-06 | |
| dc.description.abstract | The role of prolactin receptor (PRLR) during β cell adaptation to pregnancy has been extensively studied. Human epidemiological studies have revealed a potential role of prolactin outside pregnancy in maintaining glucose homeostasis. In this study, we discovered that the absence of PRLR in pancreatic β cells leads to impaired glucose tolerance in multiparous mice challenged with a high-fat diet (HFD). Unlike during pregnancy, where PRLR regulates β cell mass expansion, we observed that PRLR had a smaller role in regulating β cell mass in this model. Pancreatic islets from our knockout mice had a similar insulin secretory capacity as the wild-type mice in vitro, suggesting that an in vivo factor was responsible for the difference in glucose homeostasis. Interestingly, a difference in in vivo insulin secretion was observed when mice were challenged with oral but not intraperitoneal glucose, suggesting a defect in the incretin effect. The incretin effect, where oral glucose administration elicits a greater insulin secretory response compared to intravenous administration, is mediated by incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). We found a reduction in mRNA expressions of both incretin hormone receptors, GIP receptor (Gipr) and GLP-1 receptor (Glp-1r), in the pancreatic islets of our islet-specific PRLR knockout mice in comparison to wild-type controls after 12 weeks of HFD. Additionally, the mRNA expression of transcription factors, E2F transcription factor 1 (E2f1) and peroxisome proliferator-activated receptor-γ (Pparg), which have been shown to regulate the expressions of Gipr and Glp-1r and are downstream of PRLR, were downregulated. Together, these results suggest PRLR may have a role in the maintaining incretin effect during metabolic stress outside of pregnancy. Our findings contribute to our understanding of the complexity of PRLR in maintaining glucose homeostasis outside of pregnancy. | |
| dc.identifier.citation | Lee, D. (2024). Elucidating the role of prolactin receptor during β cell adaptation to metabolic stressors (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. | |
| dc.identifier.uri | https://hdl.handle.net/1880/118697 | |
| dc.language.iso | en | |
| dc.publisher.faculty | Cumming School of Medicine | |
| dc.publisher.institution | University of Calgary | |
| dc.rights | University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. | |
| dc.subject | Incretin effect | |
| dc.subject | Diabetes | |
| dc.subject.classification | Biochemistry | |
| dc.title | Elucidating the role of prolactin receptor during β cell adaptation to metabolic stressors | |
| dc.type | master thesis | |
| thesis.degree.discipline | Medicine – Biochemistry and Molecular Biology | |
| thesis.degree.grantor | University of Calgary | |
| thesis.degree.name | Master of Science (MSc) | |
| ucalgary.thesis.accesssetbystudent | I do not require a thesis withhold – my thesis will have open access and can be viewed and downloaded publicly as soon as possible. |